Using actinomycin as a model system for the stuy of peptide antibiotics, the following research objectives will be pursued: 1. Isolation and characterization of novel actinomycins elaborated by Streptomyces antibioticus and other Streptomyces synthesized under natural conditions or in the presence of chemically-related amino acids or amino acid analogues. Isolation and characterization of novel amino acids that are synthesized during production of new actinomycin congeners. 2. Study the biological and biochemical activities of the various novel actinomycins. 3. Study the mechanism of biosynthesis of actinomycin and of the amino acids (D-valine, sarcosine, N-methylvaline, hydroxyproline) in the antibiotic molecule using in vivo and in vitro systems. 4. Control and regulation of biosynthesis of actinomycin, a secondary metabolite. Investigations will be conducted to determine nutritional, environmental and genetic factors which regulate antibiotic peptide biosynthesis.